There is an urgent need for a method to rapidly locate pulmonary emboli (PE) as well as the source of potential further emboli, deep venous thrombi (DVT). The 9kD peptide bitistatin binds with high affinity to the glycoprotein IIb/IIIa receptor on activated platelets. When radiolabeled with 123I, bitistatin has been found to have efficacy for rapid imaging of experimental PE and DVT in an animal model. The overall goal of this project is to develop Tc-99m labeled bitistatin as a radiopharmaceutical for imaging PE and DVT. First, bitistatin will be radiolabeled with Tc-99m using HYNIC chelating agent. The behavior of Tc-99m-bitistatin will be compared with I-125-bitistatin in vitro for binding to platelets (both nonstimulated and stimulated). Stability of the label will also be studied. Second, the ability of Tc-99m- bitistatin to image DVT and PE will then be evaluated in an animal model. Image quality and tissue distribution of the Tc-99m labeled bitistatin will be determined and compared with iodinated bitistatin. Future studies will perform the safety, develop a method for large-scale production and perform testing needed prior to a clinical trial in patients with suspected thromboembolic disease. This radiopharmaceutical has potential clinical utility for rapid, direct imaging of DVT and PE. A single diagnostic imaging test which could image both types of lesions would be useful for initial diagnosis as well as for monitoring the effects of therapy. PROPOSED COMMERCIAL APPLICATION A single diagnostic test which could image both DVT and PE would be valuable for initial diagnosis as well as for monitoring the effects of therapy.